POSITIVE REGULATION OF NORMAL AND TUMORAL MAMMARY EPITHELIAL-CELL PROLIFERATION BY FIBROBLASTS IN COCULTURE

In the mammary gland, mesenchymal-epithelial interactions are of param ount importance during normal and tumoral developments. We have studie d the paracrine growth regulation of a variety of breast epithelial ce lls in coculture with normal or pathological breast fibroblasts. Two m odels of coculture were used in which the two cell types were seeded a nd grown, either together in microchamber slides or separated by a mic roporous membrane. Under these two conditions, all fibroblasts were sh own to stimulate the proliferation of the hormone-responsive breast ca rcinoma MCF-7 cell line, suggesting that cell contacts were not indisp ensable for the paracrine stimulation of MCF-7 cell growth by fibrobla sts. Moreover, in the Transwell coculture system, the proliferation of a variety of other breast carcinoma cells (MDA-MB231, T47D, and BT-20 ) was also stimulated by fibroblasts. However, the amplitude of the pr oliferative response seemed to be dependent on the carcinoma cell line considered. Moreover, the proliferative response of normal mammary ep ithelial cells to the presence of fibroblasts was shown to be signific antly higher than the tumor cell response. The nature of the tissue of fibroblast origin, normal or pathological, did not influence the grow th response of the epithelial cells. In this study, we thus demonstrat e that fibroblasts are able to stimulate the proliferation of normal a nd carcinoma cells through paracrine exchange mechanisms. We also conc lude that the target epithelial cell phenotype will essentially determ ine the extent of the proliferative response.